Common complications of sickle cell disease include severe pain episodes, recurrent lung infections, persistant leg ulsers, chronic anemia and pulmonary hypertension. Nearly one-third of sickle cell patients develop some form of pulmonary hypertension. The objects of these multi-center studies were to demonstrate if bosentan improves pulmonary vascular resistance (PVR) in patients with symptomatic pulmonary arterial hypertension (PAH) and symptomatic pulmonary hypertension (PA) associated with sickle cell disease. The study population included male and female patients with sickle cell disease (SS, S-beta-Thalassemia) age 16 and above who had pulmonary arterial hypertension or pulmonary hypertension. The secondary objectives were to evaluate the effect of bosentan on the time to clinical worsening in patients with symptomatic PH and PAH associated with SCD and to evaluate the safety and tolerability of bosentan in this patient population. During the screening for these studies, subjects underwent pulmonary function testing, 6-minute walk, an echocardiogram and a heart catheterization. Patients were randomized to receive either placebo or bosentan if they met all the inclusion criteria and none of the exclusion criteria. Those subjects with PAH were assigned to ASSET 1 and those with PH were assigned to ASSET 2. The treatment medication or placebo was administered for 4 weeks and then the dose was increase for the remaining 12 weeks. Study participants returned to the clinic once a month for safety tests and to measure 6-minute walk distance. Once a subject completed either ASSET 1 or ASSET 2 they were given the option of enrolling in the open-label study (ASSET 3) if treatment with bosentan could be beneficial. The object of ASSET 3 was to assess long-term safety, tolerability and efficacy of bosentan. Patients who met all the inclusion criteria and none of the exclusion criteria were started on 62.5 mg bid for 4 weeks and then started the maintenance dose of 125 mg bid (or stay on 62.5 mg if their weight was less than 40kg/90lbs). Patient were divided into two groups. Group A consisted of patients who began this study within 4 weeks of completing ASSET 1 or ASSET 2. Group B consisted of patients who began this study longer than 4 weeks after completing ASSET 1 or ASSET 2. Patients were to remain on drug until the FDA approved the drug for use in patients with pulmonary hypertension or until the sponsor decided to stop the study. This was a multi-center project. We enrolled 2 subjects on ASSET 1 at the NIH - other centers enrolled 11 subjects for a total of 13 subjects. We enrolled 4 subjects on ASSET 2 at the NIH - other centers enrolled 7 subjects for a total of 11 subjects. We enrolled 5 subjects on the open-labe study (ASSET 3) at the NIH - other centers enrolled 6 subjects for a total of 11. These studies are no longer enrolling subjects as the sponsor has decided to stop the studies. They currently remain open for data analysis and two manuscripts have been submitted for publication.